This is a prospective investigation of antecedent risk factors associated with incident late-onset Alzheimer's disease (AD), stroke and stroke- related dementia (SRD) in a cohort of healthy elderly, currently free of dementia and stroke, identified i stratified random sample of MEDICARE recipients from Washington Heights. The presence of key antecedent factors will have been uniformly ascertained before the start of this project, and in year 1, we shall determine, in all subjects, lipid profiles, lipoprotein (a) levels and apolipoprotein E allele frequencies. This cohort will be examined annually for incident AD, stroke and SRD, and contacted semiannually for vital health status. We shall determine relative risks associated with each antecedent factor and establish attributable risks and risk profiles for AD, stroke and SRD. We intend to investigate the following hypotheses with regard to AD: 1) that the etiology of AD is multifactorial and is likely the result of an interaction between environmental and heritable factors; 2) that advanced age, female gender, low educational and occupationally attainment and smoking are effect modifiers or intermediary factors enhancing the effect of either an environmental or inherited factor. 3) that the presence of the E4 allele of apolipoprotein E (Apo E4) will be a marker of genetic susceptibility to AD, and that exposure to putative environmental risk factors may further increase the risk of AD in these genetically susceptible individuals. We intend to investigate the following hypotheses with regard to SRD: 1) that the etiology of SRD is also multifactorial and that some of the well-accepted, conventional risk factors for stroke and for dementia will also be risk factors for SRD; 2) that advanced age and either low educational or occupational function, thus increasing the risk of SRD; 3) that a history of diabetes mellitus, hyperlipidemia or high dietary fat intake, and cardiac disease, which are accepted conventional risk factors for stroke, will be most important predictors of SRD; 4) that the presence of high levels of lipoprotein (a), a recently identified potential risk factor for atherothrombotic disease, will independently increase the risk of both stroke and SRD; 5) that a family history of dementia or stroke will be independently associated with an increased risk of SRD.
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